Abstract

While maternal mental health strongly influences neurodevelopment and health in the offspring, little is known about the determinants of inter-individual variation in the mental health of mothers. Likewise, the in utero biological pathways by which variation in maternal mental health affects offspring development remain to be defined. Previous studies implicate lipids, consistent with a known influence on cognitive and emotional function, but the relevance for maternal mental health and offspring neurodevelopment is unclear. This study characterizes the placental and circulatory lipids in antenatal depression, as well as socio-emotional outcomes in the offspring. Targeted liquid chromatography-mass spectrometry covering 470 lipid species was performed on placenta from 186 women with low (n = 70) or high (n = 116) levels of antenatal depressive symptoms assessed using the Edinburgh Postnatal Depression Scale at 26 weeks’ gestation. Child socio-emotional outcomes were assessed from the Child Behavior Check List (CBCL) at 48 months. Seventeen placental lipid species showed an inverse association with antenatal EPDS scores. Specifically, lower levels of phospholipids containing LC-PUFAs: omega-3 docosapentaenoic acid (DPA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and omega-6 arachidonic acid (AA) were significantly associated with depressive symptoms. Additional measurement of LC-PUFA in antenatal plasma samples at mid-gestation confirmed the reduced circulation of these specific fatty acids in mothers. Reduced concentration of the placental phospholipids also predicted poorer socio-emotional outcomes in the offspring. This study provides new insights into the role of the materno-fetal lipid cross-talk as a mechanism linking maternal mental health to that of the offspring. These findings show the potential utility of nutritional approaches among pregnant women with depressive symptoms to reduce offspring risk for later socio-emotional problems.

Highlights

  • Maternal depression associates with an increased risk of anxiety and depressive disorders in the offspring[1]

  • There was a distinct preponderance for phospholipids containing LC-PUFAs i.e., eicosapentaenoic acid (EPA) (C20:5, n-3), docosapentaenoic acid (DPA) (C22:5, n-3), docosahexaenoic acid (DHA) (C22:6, n-3) or arachidonic acid (AA) (C20:4, n-6). 76% of the significant lipid species contained at least one form of the stated LC-PUFAs, suggesting specificity in the associations of phospholipids containing LC-PUFAs with antenatal depressive symptoms

  • Phospholipids such as PC, PE, and PI containing polyunsaturated fatty acids like DHA, DPA, EPA, and AA had the strongest associations with antenatal depressive symptoms

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Summary

Introduction

Maternal depression associates with an increased risk of anxiety and depressive disorders in the offspring[1]. Antenatal maternal depressive symptoms associate with the structure and connectivity of cortico-limbic structures that underlie cognitive—emotional functions predictive of the risk of depression[4,5,6,7,8,9,10] Other reported biological associations of prenatal stress in offspring include changes in hypothalamo-pituitary-adrenal (HPA) axis and autonomous nervous systems[11] These effects on neural structure and connectivity as well as those on the socio-emotional development of the child are observed in community samples (i.e., normal spectrum), suggesting that the influence of maternal mood on neurodevelopment in the offspring extends across the population[12,13]. While there is compelling evidence for the association between antenatal maternal depression and socio-emotional outcomes in the offspring, the relevance in utero signal is unknown, which is a major obstacle for identifying effective interventions

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